Efficacy Study of Osimertinib in Treatment-naïve Patients With EGFR Mutant NSCLC According to TP53 Mutational Status.

NCT05785208 | Unknown Phase 4 DMC

• 1 other identifier: 4273
• Study Type: interventional
• Target: 122
• Locations: 1 country
• Sites: 11

Brief Summary

This is a prospective, biomarker-driven, open-label, clinical trial of osimertinib in treatment- naïve patients with EGFR mutant NSCLC, to evaluate the efficacy of osimertinib according to the TP53 mutational status.

Conditions

Non Small Cell Lung Cancer

Keywords

TP53; EGFR; NSCLC; Osimertinib

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) According to RECIST v1.1

  PFS is defined as the time from randomization until the date of objective disease progression using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or death (by any cause) in the absence of progression, whichever comes first.

  24 months

Secondary Outcomes (7)

• Overall Survival (OS)

  24 months

• Objective Response Rate (ORR)

  24 months

• Disease Control Rate (DCR)

  24 months

• Duration of Response (DoR)

  24 months

• Incidence and Severity of Adverse Events (AEs) according to CTCAE V5.0

  24 months

Study Arms (2)

ARM A: TP53 wilde-type

EXPERIMENTAL

Participants will receive osimertinib 80 mg once daily until disease progression or unacceptable toxicity.

Drug: Osimertinib

ARM B: TP53 mutant

EXPERIMENTAL

Participants will receive osimertinib 80 mg once daily until disease progression or unacceptable toxicity.

Drug: Osimertinib

Interventions

Osimertinib DRUG

Osimertinib will be administered at a dose of 80 mg daily until disease progression

ARM A: TP53 wilde-type; ARM B: TP53 mutant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures.
• Patients (male/female) must be \> 18 years of age.
• Locally advanced or metastatic EGFR mutant NSCLC, not amenable to curative surgery or radiotherapy with confirmation of the presence of EGFR exon 19 deletion or exon 21 p.L858R.
• Mandatory provision of an unstained, archived tumour tissue sample in a quantity sufficient to allow central analysis.
• Patients must be treatment-naïve for locally advanced or metastatic NSCLC and eligible to receive first-line treatment with osimertinib. Prior adjuvant and neo-adjuvant therapy is permitted (chemotherapy, radiotherapy) if at least 6 months has elapsed between the end of chemotherapy and enrolment.
• World Health Organization (WHO) performance status 0-2.
• Patients must have a life expectancy ≥ 12 weeks.
• Females should be using adequate contraceptive measures, should not be breastfeeding and must have a negative pregnancy test prior to start of dosing if of child- bearing potential or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening:
• Post-menopausal defined as aged more than 50 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 50 years old would be consider postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and with LH and FSH levels in the post-menopausal range for the institution.
• Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation.
• Male patients should be willing to use barrier contraception.
• Patient is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.
• At least one lesion, not previously irradiated, that can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both sponsor staff and/or staff at the study site).
• Previous treatment with osimertinib or other drugs targeting EGFR.
• Treatment with an investigational drug within five half-lives of the compound or 3 months, whichever is greater.
• Patients currently receiving (or unable to adequately stop use prior to receiving the first dose of study treatment) medications or herbal supplements included in Annex 6 (Guidance Regarding Potential Interactions with Concomitant Medications).
• Any unresolved toxicities from prior therapy greater than CTCAE grade 1 at the time of starting study treatment with the exception of alopecia and grade 2, prior platinum-therapy related neuropathy.
• Any evidence of severe or uncontrolled systemic diseases, including uncontrolled hypertension and active bleeding diatheses, which in the investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardise compliance with the protocol, or active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required.
• Patients with spinal cord compression, symptomatic and unstable brain metastases except for those patients who have completed definitive therapy, and have had a stable neurological status for at least 2 weeks after completion of definitive therapy. Patients may be on corticosteroids to control brain metastases if they have been on a stable dose for 2 weeks (14 days) prior to the start of study treatment and are clinically asymptomatic.
• Past medical history of ILD, drug-induced ILD, radiation pneumonitis requiring steroid treatment, or any evidence of clinically active ILD.
• Inadequate bone marrow reserve or organ function as demonstrated by any of the following laboratory values:
• Absolute neutrophil count \<1.5 x 109/L.
• Platelet count \<100 x 109/L.
• Haemoglobin \<90 g/L.
• Alanine aminotransferase \>2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases.
• Aspartate aminotransferase \>2.5 times ULN if no demonstrable liver metastases or \>5 times ULN in the presence of liver metastases.
• Total bilirubin \>1.5 times ULN if no liver metastases or \>3 times ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Agostino Gemelli IRCCS: lead

Study Sites (11)

Azienda Ospedaliero-Universitaria Ospedali Riuniti

Ancona, 60020, Italy

SUSPENDED

IRCCS Istituto Tumori Giovanni Paolo II

Bari, 70124, Italy

SUSPENDED

Azienda Ospedaliero-Universitaria Careggi

Florence, 50134, Italy

SUSPENDED

Ospedale Universitario di Parma

Parma, 44129, Italy

SUSPENDED

Ospedale San Camillo de Lellis

Rieti, 02100, Italy

SUSPENDED

Università Policlinico Tor Vergata

Rome, 00133, Italy

SUSPENDED

Policlinico Umberto I

Rome, 00161, Italy

SUSPENDED

Fondazione Policlinico Gemelli IRCCS

Rome, 00168, Italy

RECRUITING

Ospedale San Giovanni-Addolorata

Rome, 00184, Italy

SUSPENDED

Ospedale San Luigi

Turin, 10043, Italy

SUSPENDED

Università degli Studi di Verona

Verona, 37129, Italy

SUSPENDED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

osimertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Central Study Contacts

Emilio Bria, Professor

CONTACT

0630155202; emilio.bria@policlinicogemelli.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 27, 2023
• Study Start: June 28, 2022
• Primary Completion: February 28, 2024
• Study Completion: October 31, 2025
• Last Updated: March 27, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

IT (11)